Seeing chromosomes

Did you know that chromosomes can be seen under a light microscope, and they get their name from the fact that they are strongly stained by certain colored dyes?

I was reading through our government’s collection of educational materials on genomics. Going through the history of the gene I was startled to learn that people knew about chromosomes by the late 1800s. I had assumed they were a later discovery, requiring more sophisticated instruments than a simple light microscope.

Walther Fleming was the first to report seeing these structures while studying cell division. The dye he was using, aniline, was heavily absorbed by these mysterious granules in the nucleus, which he called chromatin. Though human chromosomes can be quite long (Chromosome 1, the longest, is 85mm long), being a single molecule (!) you can imagine it’s quite invisible even under a microscope when stretched out.

It turns out, however, that during cell division the chromosomes condense and become dense enough that a stain will make them visible under a light microscope. Since the job of the DNA in the chromosomes is to serve instructions to create proteins, it is probably important for the DNA to be “unfurled” so it has a large surface area for ready transcription. When a cell needs to divide, however, the nuclear material needs to be transported and shuffled around, and it is best to have it in a tidy ball to do so.

The study of the structure of chromosomes using microscopes is called cyto-genetics. One could imagine that the physical structure of the chromosome is not important for the understanding of the genetic code. We mostly study DNA as a one dimensional, linear sequence of characters we call the genetic code. It turns out, however, that the physical three dimensional organization of chromosomes can affect which proteins are produced and in what quantity (“gene expression”)

I’m also told that chromosomes have their own domains in the nucleus – they are not just tendrils floating willy nilly in the nucleus.

Yup, that was your small, sticky ball of biological facts from me today …


4 Replies to “Seeing chromosomes”

  1. Actually one of the very first lab protocols I ever learned was staining chromosomes for karyotyping! The tricky part turned out to be getting the chromosomes away from each other so they didn’t form a big, useless pile of unrecognizable mess. To force chromosomes apart for staining, we soaked live cells in a hypotonic buffer to make them swell like balloons, then let a single drop of buffer+cells fall 3-4 feet onto a glass slide (plenty of drops hit the floor or my shoe instead). The impact force of a successful catch exploded the swollen cells, leaving each one’s naked chromosomes spread across a small region of the slide (hence the term “metaphase spread”). Miraculously, exploded chromosomes also stick to glass, where they could be fixed in methanol, stained, and photographed.

    1. Good to hear from you Jen! That’s a fun anecdote. Do the cells have to be at a particular stage? I thought the chromosomes are normally too tenuous to be seen. I’m also impressed that the nucleus shatters with that fall – I can imagine the membrane bursts since it’s so turgid and under stress but I’d have guessed the nucleus stays intact after the fall.

  2. Great question! I neglected to mention that prior to the hypotonic buffer, cells are treated with colcemid. This halts the cell division process midway, thus increasing the subset of cells in metaphase. By metaphase, the nuclear envelope has already broken down in anticipation of chromosomal segregation to daughter cells.

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